Celldex Therapeutics' CDX-1127 Well Tolerated and Demonstrates Anti-Tumor
Activity in Phase 1 Dose-Escalation Study
Very favorable safety profile; no evidence of immune related toxicities
Three patients with significant tumor shrinkage, including an ongoing CR in
Hodgkin disease
Eight patients with stable disease or better; PFS range of 3.0 to 14+ months
Immune monitoring data in patients confirms CDX-1127 mechanism of action
PHILLIPSBURG, N.J., Nov. 7, 2013 (GLOBE NEWSWIRE) -- Celldex Therapeutics,
Inc. (Nasdaq:CLDX) today reported data from its ongoing Phase 1
dose-escalation study of the fully human monoclonal antibody CDX-1127. The
results suggest an excellent safety profile and demonstrate clear biologic
activity and promising signs of clinical activity in an advanced, refractory
patient population. No maximum tolerated dose has been reached to date. The
data will be presented in two poster sessions (poster #144 and 146) at the
2013 Society for Immunotherapy of Cancer (SITC) Annual Meeting, November 7 –
10, 2013. In addition, a third poster (#85) will be presented on preclinical
combination studies of CDX-1127 with chemotherapies and checkpoint inhibitors.
The Company will host a webcast/conference call at 8:30 am ET today to discuss
the results (details provided below).
"CDX-1127 has exceeded our expectations thus far in this ongoing Phase 1
dose-escalation study," said Thomas Davis, MD, Senior Vice President and Chief
Medical Officer of Celldex Therapeutics. "Our primary goal was to establish a
favorable safety profile, a challenge that other agonist antibodies in this
class have not been able to meet. To date, CDX-1127 has demonstrated minimal
toxicity and, importantly, no evidence of worrisome overlap with toxicities
seen with other immunotherapies—a critical hurdle for combination therapy. We
were also very pleased to see clear evidence of biologic and anti-cancer
activity in a heavily pretreated patient population. While future data from
the expansion cohorts will be important to understanding single-agent
activity, we are confident based on the dose-escalation data we have seen to
date that we are well positioned to initiate combination studies of CDX-1127,
with a particular interest in immune modulators."
"We are encouraged by the initial safety and activity profile observed to date
and believe CDX-1127 could play an important role in the field of cancer
immunotherapy," said Howard A. "Skip" Burris, III, MD, Chief Medical Officer
and Executive Director of the Drug Development Program at Sarah Cannon
Research Institute and a lead investigator of the Phase 1 CDX-1127 study. "An
agonist with this safety and biologic activity profile has potential,
particularly in combination with checkpoint inhibitors, where the ability to
mount an immune response could expand the effectiveness of these compounds for
more patients."
CDX-1127 is a fully human monoclonal antibody that targets CD27, a critical
molecule in the activation pathway of lymphocytes. CD27 can be effectively
manipulated with activating antibodies to induce potent anti-tumor responses,
and may result in less toxicities due to its restricted expression and
regulation. CDX-1127 is a potent anti-CD27 agonist that induces activation and
proliferation of human T cells when combined with T-cell receptor stimulation.
In lymphoid malignancies that express CD27 at high levels, CDX-1127 has an
additional mechanism through a direct anti-tumor effect.
Study Overview:
The Phase 1 dose-escalation study of CDX-1127 includes two arms—solid tumors
and lymphoid malignancies and is designed to evaluate five doses (0.1, 0.3, 1,
3, 10 mg/kg). Enrollment is complete in the solid tumor dose-escalation arm
(n=25) and expansion cohorts are ongoing in metastatic melanoma and renal cell
carcinoma. In the dose-escalation lymphoid malignancies arm (n=17), enrollment
recently initiated in the 10 mg/kg cohort and expanded development is being
planned. Currently, first response assessments are pending for four patients
across the 1 and 3 mg/kg cohorts and all patients in the 10 mg/kg cohort in
the lymphoid malignancies arm. Patients enrolled in the study across both arms
had advanced disease and most were heavily pretreated. Patients progressed on
previous therapies and had no remaining approved treatment options before
study entry. The median number of prior therapies is 5 anti-cancer (3
cytotoxic) for solid tumors and 4 anti-cancer (3 cytotoxic) for lymphoid
malignancies.
Safety and Immune Monitoring Overview:
In the solid tumor dose-escalation phase, CDX-1127 was associated with minimal
toxicity including at the highest dose levels through multiple cycles. No
maximum tolerated dose was reached. The most common treatment-related adverse
events were decreased appetite (12%) and fatigue (12%). One patient
experienced a dose limiting toxicity (DLT), a Grade 3 transient asymptomatic
hyponatremia 14 days after a single 1.0 mg/kg dose of CDX-1127. Hyponatremia
has not been attributed to CDX-1127 in any other patient. The safety data from
the lymphoid malignancies arm also show that CDX-1127 has been well tolerated
with no DLTs to date.
The preliminary assessment of pharmacokinetics demonstrates significant
exposure to CDX-1127 throughout the duration of the study period. Immune
monitoring assessments conducted in the solid tumor arm support the overall
safety profile and also demonstrate that CDX-1127 induces immunologic activity
in patients that is consistent with both its mechanism of action and
preclinical models, including an increase in Natural Killer cells and in T
cells that express the activation marker, HLA-DR. The study also identified
the serum chemokine, interferon-gamma inducible protein 10 (IP-10) as a
significant biomarker for CDX-1127 treatment. Of note, the study confirms that
CDX-1127 does not induce major lymphocyte depletion, but does reduce the
number of regulatory T cells, which are thought to have immune suppressive
activity. Taken together, these markers demonstrate clear evidence of
lymphocyte activation—the direct purpose of CDX-1127 therapy.
Clinical Activity Overview:
Across both arms, eight patients experienced stable disease or better with a
PFS range of 3.0 to 14+ months. In addition, three patients experienced
significant tumor shrinkage, including a complete response as outlined below.
*A 28 year old female with Stage IV Hodgkin lymphoma achieved a complete
response, including complete resolution of B symptoms (drenching sweats,
pruritus and weight loss)—an important marker of disease activity in
Hodgkin disease, after three cycles of CDX-1127 (0.3 mg/kg). The patient
remains in remission at 8.6+ months. During treatment, the area of
measurable lesions first increased and then regressed. This pattern is
consistent with the current perception of an immune mediated response. The
patient was heavily pretreated, including high dose chemotherapy with
autologous marrow transplantation, and most recently had progressed after
less than one month on Adcetris™ plus chemotherapy.
*A 69 year old male with Stage IV colorectal cancer metastatic to the
liver, lung and peritoneum was treated with CDX-1127 (1 mg/kg) and had a
33% unidimensional shrinkage of measurable disease and a PFS of 5.7
months. The shrinkage was associated with small, new lesions representing
a mixed response. The patient had previously received multiple agents,
including Avastin® and most recently had progressed through
Xeloda®/radiation at two weeks.
*A 67 year old male with Stage III marginal zone B-cell lymphoma who
received CDX-1127 (0.3 mg/kg) experienced a 36% shrinkage of measurable
disease, including complete disappearance of disease in the inguinal and
iliac regions and had a PFS of 5.6 months. The patient was very heavily
pretreated with 10 prior regimens of cytotoxic, radiation and Rituxan®
therapy.
Two patients received all five cycles of treatment and were on trial for
greater than a year, including:
*An 83 year old male with Stage IV renal cell carcinoma metastatic to liver
and lung who remains progression-free at 14+ months after study entry, and
*A 52 year old male with Stage IV follicular lymphoma who had a PFS of 14
months.
The Company also reported very early data from the solid tumor expansion
cohorts, where CDX-1127 has been well-tolerated to date. The melanoma cohort
has accrued 14 patients at 3 mg/kg with eight patients continuing treatment,
seven who have not yet been seen for the first assessment of response. One
patient with uveal melanoma who is entering the third round of treatment has
experienced a 12% shrinkage of measurable disease by RECIST and stable disease
is ongoing at 5.7 months. The renal cell carcinoma arm has accrued eight
patients at 3 mg/kg with seven continuing treatment, all of whom have not yet
been seen for the first assessment of response.
In a separate poster, the Company reported new data of CDX-1127 in combination
therapy using mouse tumor models. Agents that induce tumor killing to provide
a source of antigen and agents that block T cell inhibitory molecules were
chosen for their potentially complementary mechanisms of action. Employing
challenging treatment settings where single agent activity is limited, a clear
survival benefit was observed with CDX-1127 combinations of cyclophosphamide
or checkpoint blockade. These studies, together with the favorable safety
profile and activity data from the Phase 1 trial with CDX-1127, support the
initiation of combination trials with conventional and immune-based therapies.
Webcast/Conference Call Information:
Celldex management will host a conference call/webcast at 8:30 am ET today to
discuss the CDX-1127 program. Mario Sznol, MD, Professor, Internal Medicine,
Vice-Chief, Section of Medical Oncology, Co-director, Yale Spore in Skin
Cancer and Translational Research Leader, Melanoma Program at Yale Cancer
Center and Dr. Madhav Dhodapkar, MBBS, Professor of Medicine and Chief,
Section of Hematology at Yale Cancer Center will join the call.
The conference call and presentation will be webcast live over the Internet
and can be accessed by logging on to the Events & Presentations section under
"Investors and Media" of the Celldex Therapeutics website at www.celldex.com.
The call can also be accessed by dialing (866) 743-9666 (within the United
States) or (760) 298-5103 (outside the United States). The passcode is
93902541.
A replay of the call will be available approximately one week after the live
call concludes through November 14, 2013. To access the replay, dial
855-859-2056 (within the United States) or 404-537-3406 (outside the United
States). The passcode is 93902541. The webcast will also be archived on the
Company's website.
Adcetris is a registered trademark of Seattle Genetics; Avastin and Xeloda are
registered trademarks of Roche; Rituxan is a registered trademark of Biogen.
About Celldex Therapeutics, Inc.
Celldex is developing targeted therapeutics to address devastating diseases
for which available treatments are inadequate. Our pipeline is built from a
proprietary portfolio of antibodies and immunomodulators used alone and in
strategic combinations to create novel, disease-specific therapies that
induce, enhance or suppress the body's immune response. Visit www.celldex.com.
Safe Harbor Statement Under the Private Securities Litigation Reform Act of
1995: This release contains "forward-looking statements" made pursuant to the
safe harbor provisions of the Private Securities Litigation Reform Act of
1995, including those related to the Company's strategic focus and the future
development and commercialization (by Celldex and others) of rindopepimut
(CDX-110), Glembatumumab vedotin ("glemba"; CDX-011), CDX-1135, CDX-1401,
CDX-1127, CDX-301, Belinostat and other products. Forward-looking statements
reflect management's current knowledge, assumptions, judgment and expectations
regarding future performance or events. Although management believes that the
expectations reflected in such statements are reasonable, they give no
assurance that such expectations will prove to be correct and you should be
aware that actual results could differ materially from those contained in the
forward-looking statements. Forward-looking statements are subject to a number
of risks and uncertainties, including, but not limited to, our ability to
successfully complete research and further development and commercialization
of rindopepimut, glemba and other drug candidates, our ability to obtain
additional capital to meet our long-term liquidity needs on acceptable terms,
or at all, including the additional capital which will be necessary to
complete the clinical trials that we have initiated or plan to initiate; our
ability to adapt our APC Targeting Technology^TM to develop new, safe and
effective vaccines against oncology and infectious disease indications; our
ability to successfully complete product research and further development of
our programs; the uncertainties inherent in clinical testing; our limited
experience in bringing programs through Phase 3 clinical trials; our ability
to manage research and development efforts for multiple products at varying
stages of development; the timing, cost and uncertainty of obtaining
regulatory approvals; the failure of the market for the Company's programs to
continue to develop; our ability to protect the Company's intellectual
property; the loss of any executive officers or key personnel or consultants;
competition; changes in the regulatory landscape or the imposition of
regulations that affect the Company's products; and other factors listed under
"Risk Factors" in our annual report on Form 10-K.
All forward-looking statements are expressly qualified in their entirety by
this cautionary notice. You are cautioned not to place undue reliance on any
forward-looking statements, which speak only as of the date of this release.
We have no obligation, and expressly disclaim any obligation, to update,
revise or correct any of the forward-looking statements, whether as a result
of new information, future events or otherwise.
CONTACT: Sarah Cavanaugh
Vice President of Investor Relations &
Corp Communications
Celldex Therapeutics, Inc.
(781) 433-3161
scavanaugh@celldex.com